Curative effect and safety of haploidentical allogeneic cytokine-induced killer in treatment of advanced hepatocellular carcinoma
-
摘要:
目的 探讨同种异体半相合细胞因子诱导的杀伤(CIK)细胞治疗晚期肝癌的疗效及安全性。 方法 采集21例晚期肝细胞癌(肝癌)患者健康一级直系亲属的外周血单个核细胞, 在体外诱导成异体半相合CIK细胞后回输给患者, 回输4个周期。评估治疗效果和安全性。 结果 随访半年, 21例患者的存活率为81%(17/21), 疾病稳定患者11例, 疾病进展患者10例(含4例死亡病例)。6例患者治疗期间出现不同程度的发热, 1例出现皮疹。与治疗前相比, 患者治疗后第4周期的血小板数量降低, 差异有统计学意义(P < 0.05), 而患者治疗后第1、4周期的白细胞、中性粒细胞、淋巴细胞、血红蛋白, 肝、肾功能差异均无统计学意义(均为P>0.05)。 结论 同种异体半相合CIK细胞治疗晚期肝癌患者能够有效改善生活质量, 不良反应大都在可耐受范围, 是一种较安全的治疗方法。 -
关键词:
- 同种异体半相合 /
- 细胞因子诱导的杀伤细胞 /
- 肝细胞癌 /
- 不良反应 /
- 细胞治疗
Abstract:Objective To investigate the curative effect and safety of haploidentical allogeneic cytokine-induced killer (CIK) in treatment of advanced hepatocellular carcinoma. Methods The peripheral blood mononuclear cell (PBMC) of the healthy immediate family members of 21 patients with advanced hepatocellular carcinoma (HCC) were collected, induced into haploidentical allogeneic CIK in vitro and transfused to the patients for 4 cycles. The curative effect and safety were assessed. Results The 21 patients were followed up for half a year. The survival rate was 81% (17/21). Among the 21 patients, 11 cases were with stable disease and 10 cases were with progressive disease(including 4 dead cases). Six patients developed fever of different degrees during the treatment and one patient developed rash. The platelet counts of the patients at the fourth cycle after the treatment decreased compared with that before the treatment, with significance difference (P < 0.05). The difference in leukocytes, neutrophils, lymphocytes, hemoglobin, liver function and renal function at the first and fourth cycle after the treatment had no statistical significance (all in P>0.05). Conclusions Haploidentical allogeneic CIK in treatment of advanced HCC may effectively improve the quality of life and the adverse reactions are tolerable, which is a relatively safe therapy. -
表 1 21例患者治疗前后血常规的变化
Table 1. Changes of blood routine examination of 21 patients before and after treatment(x±s)
指标 治疗前 治疗后
第1周期治疗后
第4周期白细胞总数(×109/L) 5.3±2.5 5.1±1.7 4.8±2.9 中性粒细胞(×109/L) 3.7±1.4 3.3±1.2 3.1±1.0 淋巴细胞(×109/L) 1.0±0.6 1.2±0.7 1.1±0.6 血小板计数(×109/L) 172±88 146±85 111±43a 血红蛋白(g/L) 112±16 116±17 120±19 注:与治疗前比较,aP < 0.05 表 2 21例患者治疗前后肝、肾功能的变化
Table 2. Changes of liver and renal functions of 21 patients before and after treatment(x±s)
指标 治疗前 治疗后
第1周期治疗后
第4周期总蛋白(g/L) 66±8 66±6 65±6 白蛋白(g/L) 37±4 37±5 37±6 天冬氨酸转氨酶(U/L) 41±22 43±22 46±20 丙氨酸转氨酶(U/L) 42±9 36±20 34±14 总胆红素(μmol/L) 16±6 17±5 19±6 直接胆红素(μmol/L) 8±3 8±3 8±3 血清肌酐(μmol/L) 69±15 68±13 70±15 血尿素氮(mmol/L) 4.0±1.3 3.8±1.3 4.5±1.6 -
[1] Jäkel CE, Schmidt-Wolf IG. An update on new adoptive immunotherapy strategies for solid tumors with cytokine-induced killer cells[J]. Expert Opin Biol Ther, 2014, 14(7):905-916. doi: 10.1517/14712598.2014.900537 [2] Yu X, Zhao H, Liu L, et al. A randomized phase Ⅱ study of autologous cytokine-induced killer cells in treatment of hepatocellular carcinoma[J]. J Clin Immunol, 2014, 34(2):194-203. doi: 10.1007/s10875-013-9976-0 [3] Yan CX, Zhang HM, Chen R, et al. Adverse reactions and their management in the treatment of malignant tumors using cytokine-induced killer cells[J]. Ann Palliat Med, 2013, 2(2):85-89. http://cn.bing.com/academic/profile?id=125564733&encoded=0&v=paper_preview&mkt=zh-cn [4] Chen R, Deng X, Wu H, et al. Combined immunotherapy with dendritic cells and cytokine-induced killer cells for malignant tumors:a systematic review and meta-analysis[J]. Int Immunopharmacol, 2014, 22(2):451-464. doi: 10.1016/j.intimp.2014.07.019 [5] Mesiano G, Todorovic M, Gammaitoni L, et al. Cytokine-induced killer (CIK) cells as feasible and effective adoptive immunotherapy for the treatment of solid tumors[J]. Expert Opin Biol Ther, 2012, 12(6):673-684. doi: 10.1517/14712598.2012.675323 [6] 庞佳楠, 崔久嵬.细胞因子诱导的杀伤细胞治疗肿瘤的研究进展[J/CD].中华临床医师杂志:电子版, 2014, 8(15):2889-2993.Pang JN, Cui JW. Progress of cytokine-induced killer cells therapy in cancer[J/CD]. Chin J Clin:Electr Edit, 2014, 8(15):2889-2993. [7] Lee JH, Lee JH, Lim YS, et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma[J]. Gastroenterology, 2015, 148(7):1383-1391. doi: 10.1053/j.gastro.2015.02.055 [8] Pan K, Li YQ, Wang W, et al. The efficacy of cytokine-induced killer cell infusion as an adjuvant therapy for postoperative hepatocellular carcinoma patients[J]. Ann Surg Oncol, 2013, 20(13):4305-4311. doi: 10.1245/s10434-013-3144-x [9] 杨旭, 许光, 雷振, 等. RECIST1. 1与WHO, RECIST1. 0标准评价周边型肺癌疗效比较[J].中国医学影像学杂志, 2012, 20(5):355-358. http://www.cnki.com.cn/Article/CJFDTOTAL-ZYYZ201205013.htmYang X, Xu G, Lei Z, et al. Comparison of RECIST 1.1, RECIST 1.0 and WHO criteria for peripheral lung cancer response to treatment[J]. Chin J Med Imaging, 2012, 20(5):355-358. http://www.cnki.com.cn/Article/CJFDTOTAL-ZYYZ201205013.htm [10] Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer[J]. Science, 2015, 348(6230):62-68. doi: 10.1126/science.aaa4967 [11] 何志惠, 桑圣刚, 洪涛, 等. DC-CIK细胞治疗对晚期恶性肿瘤患者免疫功能及生活质量的影响[J].肿瘤预防与治疗, 2013, 26(4):213-215. http://www.cqvip.com/qk/97313b/201304/47110780.htmlHe ZH, Sang SG, Hong T, et al. The effects of DC and CIK cell treatment on the quality of life and immune function in patients with advanced cancer[J]. J Cancer Contr Treat, 2013, 26(4):213-215. http://www.cqvip.com/qk/97313b/201304/47110780.html [12] Rosenberg SA, Restifo NP, Yang JC, et al. Adoptive cell transfer:a clinical path to effective cancer immunotherapy[J]. Nat Rev Cancer, 2008, 8(4):299-308. doi: 10.1038/nrc2355 [13] Matsueda S, Graham DY. Immunotherapy in gastric cancer[J]. World J Gastroenterol, 2014, 20(7):1657-1666. doi: 10.3748/wjg.v20.i7.1657 [14] Qian S, Shi P, Xie Y, et al. Clinical study of autologous cytokine-induced killer cells for the consolidation treatment of elderly patients with diffuse large B-cell lymphoma[J]. Blood, 2014, 124(21):4463-4463. http://cn.bing.com/academic/profile?id=2523141632&encoded=0&v=paper_preview&mkt=zh-cn [15] Rettinger E, Huenecke S, Pfirrmann V, et al. Repetitive infusions of cytokine-induced killer (CIK) cells for treatment of impending relapse in high-risk leukemia patients after allogeneic stem cell transplantation[J]. Blood, 2014, 124(21):2438-2438. http://cn.bing.com/academic/profile?id=2395952765&encoded=0&v=paper_preview&mkt=zh-cn [16] 杨帆, 张琪, 陈规划.肝癌细胞免疫治疗进展[J].外科研究与新技术, 2013, 2(4):262-266. http://www.cnki.com.cn/Article/CJFDTOTAL-TJYE201304015.htmYang F, Zhang Q, Chen GH. Cellular immunotherapy of hepatocellar carcinoma[J]. Surg Res New Tech, 2013, 2(4):262-266. http://www.cnki.com.cn/Article/CJFDTOTAL-TJYE201304015.htm [17] Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting:integrating immunity's roles in cancer suppression and promotion[J]. Science, 2011, 331(6024):1565-1570. doi: 10.1126/science.1203486 [18] 王士勇, 张晖, 杜微丽, 等.纤维连接蛋白诱导CIK细胞治疗晚期癌症患者的安全性及疗效评价[J].中国肿瘤临床, 2009, 36(20):1163-1166. http://www.cnki.com.cn/Article/CJFDTOTAL-ZGZL200920007.htmWang SY, Zhang H, Du WL, et al. Therapeutic safety and effects of cytokine induced killer cells activated by retronectin for advanced cancer patients[J]. Chin J Clin Oncol, 2009, 36(20):1163-1166. http://www.cnki.com.cn/Article/CJFDTOTAL-ZGZL200920007.htm
计量
- 文章访问数: 74
- HTML全文浏览量: 51
- PDF下载量: 3
- 被引次数: 0